Evidence map›Paper›PMID 31295152›Full record

Trial reportClinical and translational gastroenterology2019

A Phase 2 Study of Galunisertib (TGF-β1 Receptor Type I Inhibitor) and Sorafenib in Patients With Advanced Hepatocellular Carcinoma.

R K Kelley, E Gane, E Assenat, J Siebler, P R Galle, P Merle, I O Hourmand, A Cleverly, Y Zhao, I Gueorguieva and 4 more

Abstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical and translational gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
166citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

166 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  7. Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026
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  11. Targeting Tumor-Associated Macrophages and Cancer-Associated Fibroblasts to Overcome Therapeutic Resistance in Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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106 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

R K KelleyUniversity of California, San Francisco, San Francisco, California, USA.
E GaneAuckland City Hospital, Grafton, Auckland, New Zealand.
E AssenatCentre Hospitalier Régional Universitaire (CHU) de Montpellier, Montpellier, France.
J SieblerFriedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
P R GalleUniversity Medical Center Mainz, Mainz, Germany.
P MerleHépatologie, Groupement Hospitalier Lyon Nord, France.
I O HourmandService d'Hépatogastroentérologie, CHU, Caen, France.
A CleverlyEli Lilly and Company, Erl Wood, UK.
Y ZhaoEli Lilly and Company, Indianapolis, Indiana, USA.
I GueorguievaEli Lilly and Company, Erl Wood, UK.
M LahnEli Lilly and Company, Indianapolis, Indiana, USA.
S FaivreHospital Beaujon, Clichy, France.
K A BenhadjiEli Lilly and Company, Indianapolis, Indiana, USA.
G GiannelliNational Institute of Gastroenterology, "s. De Bellis" Research Hospital, Castellana Grotte, Bari, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionInhibition of tumor growth factor-β (TGF-β) receptor type I potentiated the activity of sorafenib in preclinical models of hepatocellular carcinoma (HCC). Galunisertib is a small-molecule selective inhibitor of TGF-β1 receptor type I, which demonstrated activity in a phase 2 trial as second-line HCC treatment.

methodsThe combination of galunisertib and sorafenib (400 mg BID) was tested in patients with advanced HCC and Child-Pugh A liver function without prior systemic therapy. Galunisertib dose was administered 80 or 150 mg b.i.d. orally for 14 days every 28 days in safety lead-in cohorts; in the expansion cohort, all patients received galunisertib 150 mg b.i.d. Objectives included time-to-tumor progression, changes in circulating alpha fetoprotein and TGF-β1, safety, overall survival (OS), response rate, and pharmacokinetics (PK).

resultsPatients (n = 47) were enrolled from 5 non-Asian countries; 3 and 44 patients received the 80 mg and 150 mg b.i.d. doses of galunisertib, respectively. The pharmacokinetics and safety profiles were consistent with monotherapy of each drug. For the 150 mg b.i.d. galunisertib cohort, the median time-to-tumor progression was 4.1 months; the median OS was 18.8 months. A partial response was seen in 2 patients, stable disease in 21, and progressive disease in 13. TGF-β1 responders (decrease of >20% from baseline) vs nonresponders had longer OS (22.8 vs 12.0 months, P = 0.038). DISCUSSION: The combination of galunisertib and sorafenib showed acceptable safety and a prolonged OS outcome.

Indexed as

Administration, OralAdultAgedAged, 80 and overalpha-FetoproteinsCarcinoma, HepatocellularCase-Control StudiesDisease ProgressionDrug Therapy, CombinationFemaleHumansLiver NeoplasmsMaleMiddle AgedProtein Kinase InhibitorsPyrazolesAFP protein, humanalpha-FetoproteinsLY-2157299Protein Kinase InhibitorsPyrazolesQuinolinesReceptors, Transforming Growth Factor betaSorafenibTGFB1 protein, humanTransforming Growth Factor beta1

Identifiers

PMID31295152
PMCPMC6708671

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.